Background: Developmental difficulties, muscle hypotonia, small stature, unique facial traits, and congenital abnormalities, notably cardiac, are all phenotypic aspects of Down syndrome. Aim and objectives: to assess thyroid function abnormalities in children with Down syndrome and congenital heart disease. Subjects and methods: The study was conducted at Cardiology Unit of Pediatric and Neonatology Department at Zagazig University Hospitals as a cross-sectional study on 50 subjects, Patients were evaluated for congenital heart disease using plain chest X-ray, electrocardiography, two-dimensional echocardiography and Doppler studies. Thyroid function parameters were also performed including plasma TSH, FT3 and FT4. Results: Highly significant differences were found between the studied groups as regard TSH, FT4 and FT3 levels, but no statistically significant differences between them as regard age or gender. In addition, there was no significant relation between genetic types of Down syndrome and thyroid function. Conclusion: Thyroid dysfunctions, most commonly subclinical hypothyroidism, are frequent in children with Down syndrome, with no relation of length, weight, maternal age or gender to the thyroid function.